Qualitative and quantitative contrast-enhanced ultrasonography for the characterisation of non-palpable testicular tumours.

AIM: To assess the diagnostic performance of conventional ultrasound (US) and contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of non-palpable intratesticular tumours. MATERIALS AND METHODS: The local ethics review board approved the protocol, and all of the patients provided written informed consent. Between December 2011 and February 2014, men with non-palpable testicular tumours and normal tumour markers who were referred for surgery were included. The tumours were analysed by conventional US, including B-mode and colour Doppler US (CDUS) as well as by CEUS. Morphological aspects and qualitative and quantitative CEUS criteria, based on visual enhancement and time-intensity curves, were assessed for each lesion. RESULTS: Forty patients were ultimately included. Based on histopathological results, the tumours were classified into three groups: benign tumours (n=16), malignant tumours (n=15), and burned-out tumours (n=9). In B-mode, the morphological aspects were significantly different between benign and malignant tumours (p-values from 0.0002 to 0.008). Qualitative and quantitative analyses of the CEUS images revealed that burned-out tumours exhibited significantly less enhancement than malignant and benign tumours: in burned-out tumours, time-intensity curves were flat, whereas in both benign and malignant tumours the curves had a bell-shaped pattern. All intensity parameters were lower for burned-out tumours compared to benign and malignant tumours (p-value from 0.0001 to 0.026). Both benign and malignant tumours enhanced strongly, however, and no significant difference between the two was noted (p-value from 0.0721 to 0.0953). CONCLUSION: Unlike conventional US, which enable benign lesions to be differentiated from malignant or burned-out tumours, CEUS failed to enabled differentiation between benign lesions and malignant vascularised testicular tumours. CEUS appears to have the potential, however, to differentiate burned-out tumours from vascularised testicular tumours.

Neonatal brain MRI: how reliable is the radiologist's eye?

INTRODUCTION: White matter (WM) analysis in neonatal brain magnetic resonance imaging (MRI) is challenging, as demonstrated by the issue of diffuse excessive high signal intensity (DEHSI). We evaluated the reliability of the radiologist's eye in this context. METHODS: Three experienced observers graded the WM signal intensity on axial T2-weighted 1.5T images from 60 different premature newborns on 2 occasions 4 weeks apart with a semi-quantitative classification under identical viewing conditions. RESULTS: The intra- and inter-observer correlation coefficients were fair to moderate (Fleiss' kappa between 0.21 and 0.60). CONCLUSION: This is a serious limitation of which we need to be aware, as it can lead to contradictory conclusions in the challenging context of term-equivalent age brain MRI in premature infants. These results highlight the need for a semiautomatic tool to help in objectively analyzing MRI signal intensity in the neonatal brain.

Non-disclosure of a pregnant woman's HIV status to her partner is associated with non-optimal prevention of mother-to-child transmission.

Our objective was to study relations between non-disclosure of HIV to partner, socio demographics and prevention of HIV mother-to-child transmission (PMTCT), among HIV-infected pregnant women enrolled in the French Perinatal Cohort (ANRS-EPF-CO1) from 2005 to 2009 (N = 2,952). Fifteen percent of the women did not disclose their HIV status to their partner. Non-disclosure was more frequent in women diagnosed with HIV infection late in pregnancy, originating from Sub-Saharan Africa or living alone, as well as when the partner was not tested for HIV. Non-disclosure was independently associated with non optimal PMTCT: late initiation of antiretroviral therapy, detectable viral load at delivery and lack of neonatal prophylaxis. Nonetheless, the rate of transmission did not differ according to disclosure status. Factors associated with non-disclosure reflect vulnerability and its association with non optimal PMTCT is a cause for concern although the impact on transmission was limited in this context of universal free access to care.

Factors associated with hospital admission and adverse outcome for COVID-19: Role of social factors and medical care.

BACKGROUND: Beyond sex, age, and various comorbidities, geographical origin and socioeconomic deprivation are associated with Coronavirus Disease (COVID-19) morbidity and mortality in the general population. We aimed to assess factors associated with severe forms of COVID-19 after a hospital emergency department visit, focusing on socioeconomic factors. METHODS: Patients with laboratory-confirmed COVID-19 attending the emergency department of Béclère Hospital (France) in March-April 2020 were included. Postal addresses were used to obtain two geographical deprivation indices at the neighborhood level. Factors associated with hospitalization and factors associated with adverse outcomes, i.e. mechanical ventilation or death, were studied using logistic and Cox analyses, respectively. RESULTS: Among 399 included patients, 321 were hospitalized. Neither geographical origin nor socioeconomic deprivation was associated with any of the outcomes. Being male, older, overweight or obese, diabetic, or having a neuropsychiatric disorder were independent risk factors for hospitalization. Among 296 patients hospitalized at Béclère Hospital, 91 experienced an adverse outcome. Older age, being overweight or obese, desaturation and extent of chest CT scan lesions>25% at admission (aHR: 2.2 [95% CI: 1.3-3.5]) and higher peak CRP levels and acute kidney failure (aHR: 2.0 [1.2-3.3]) during follow-up were independently associated with adverse outcomes, whereas treatment with hydrocortisone reduced the risk of mechanical ventilation or death by half (aHR: 0.5 [0.3-0.8]). CONCLUSION: No association between geographical origin or socioeconomic deprivation and the occurrence of a severe form of COVID-19 was observed in our population after arrival to the emergency department. Empirical corticosteroid use with hydrocortisone had a strong protective impact.

Tolerance of efavirenz in children.

OBJECTIVE: To extend the limited knowledge of efavirenz tolerance in children. METHOD: An observational study of 33 children given efavirenz combined with various others agents and followed in a single institution. RESULTS: Fifteen (42%) of the children presented at least one clinically discernable side effect, cutaneous (n = 5), nervous system (n = 10), or both (n = 2). Intolerance led to treatment interruption in seven children but the main symptom was transitory dizziness or other signs similar to those observed in adults. CONCLUSION: Early, often transient nervous system side effects require careful preparation with the child and his family to avoid premature and inadequate withdrawal from treatment.

Frequent detection of HIV-1 in the gastric aspirates of neonates born to HIV-infected mothers.

OBJECTIVE: To evaluate the frequency and correlates of oral route exposure of infants born to HIV-1-infected women. METHODS: A multicenter study was performed within the prospective French Perinatal Cohort Study of mother-to-child HIV transmission. Oropharyngeal and gastric aspirates from 122 neonates were studied by reverse transcriptase (RT) polymerase chain reaction (PCR) for the presence of HIV-1, as well as for standard microbiology (Gram staining and culture). RESULTS: Aspirates from 101 neonates were analyzed by RT-PCR; 28% of these were positive for HIV RNA. Another 21 aspirates could not be tested because of PCR inhibition. The median concentration of HIV RNA in the positive aspirates was 126 copies/ml (range: 8-1270). Detection of HIV-1 in the aspirate was significantly related to high maternal plasma-viral load, presence of blood in the aspirate, positive Gram stain or culture, episiotomy or perineal lesions, and sexually transmitted infections during the pregnancy. Most of the mothers received zidovudine prophylaxis during pregnancy and delivery. Among the six infants who were infected with HIV, three had positive aspirates. Of the three assumed to have acquired the infection intrapartum, only one had an HIV RNA-positive aspirate. CONCLUSION: Exposure of the fetus to HIV via the oral route occurs frequently, even in the presence of zidovudine prophylaxis, and is likely to be one of the mechanisms of intrapartum transmission, but not the only one.

Early HIV-specific cytotoxic T lymphocytes and disease progression in children born to HIV-infected mothers.

The activities of HIV-specific cytotoxic T lymphocytes (CTLs) were evaluated in 10 HIV-infected children, born to infected mothers who did not receive AZT during pregnancy. CTL activities were present as early as 4 months of age. The five children that progressed to AIDS before 1 year of age had reduced in vivo and in vitro CTL activities, when compared with children who remained AIDS free after 1 year of age. The latter children had weak in vivo activated CTL responses but strong memory CTLs. No relation was found between viral load, lymphocyte populations, and CTL responses between birth and 6 months of age. Between 7 and 12 months old, children with broader in vitro activated CTLs had higher absolute numbers of CD4+ and CD8+ T lymphocytes and lower plasma viral load. These data support a beneficial role of CTLs in pediatric HIV infection.

Psychological characteristics of infertile patients: discriminating etiological factors from reactive changes.

Our objective was to discriminate psychological factors playing an etiological role in infertility and psychological problems as consequences of infertility. The design was a prospective study of couples with initially Undetermined Fertility (UF couples) and couples with initially Known Infertility (KI couples). After a 13-month follow-up, three groups could be defined: fertile UF couples; infertile UF couples; and KI couples. Hypotheses were the following. If a psychological factor played an etiological role, measures in fertile UF couples should be different from measures in infertile UF couples and in KI couples. If a psychological measure reflected a reactive change, KI couples should differ from both groups of UF couples. Finally, if a psychological variable played both roles, the three pairwise comparisons between groups should reveal differences, with the largest difference between fertile UF couples and KI couples. The questionnaires used were the Child Project Questionnaire (CPQ), with three factor scores (different for men and women) and a Sexual Problems Score (SPS); the Dyadic Adjustment Scale; the State-Trait Anxiety Inventory; the Neonatal Perception Inventory. In women, on CPQ factor II, i.e. Frequency of Thoughts and Concerns related to the Project to Conceive a Child and on the SPS, KI women had scores significantly higher than both groups of UF women. In men, on CPQ factor II, i.e. Quality of Integration between Wish for a Child and Sexuality, men from fertile UF couples had significantly higher scores than men from both infertile groups; the two latter groups did not differ significantly. On the SPS, scores of men from infertile UF couples and scores of men from KI couples were significantly higher than scores of men from fertile UF couples; scores were similar in both groups of men from infertile couples. We conclude that in women, CPQ factor II and sexual problems reflected reactive changes to infertility and that in men CPQ factor II and sexual problems represented etiological factors.

Psychological factors in the aetiology of infertility: a prospective cohort study.

The objectives were to identify and measure psychological factors characterizing the period following the cessation of contraception and to assess these psychological factors as predictors of the couples' fertility. A cohort of 63 couples with initially undetermined fertility status was prospectively studied, first shortly after the cessation of contraception, then 13 months later. The Child Project Questionnaire was constructed to assess psychological variations following the cessation of contraception. An Interspouse Difference Score was constructed to measure the difference between the spouses' responses. Three male and three female factors were derived from the questionnaire. The Interspouse Difference Score was significantly greater in infertile than in fertile couples. Two psychological factor scores were significantly higher in fertile subjects: the wives' level of positive expectations related to motherhood, and the husbands' quality of integration between the wish for a child and sexual relationships. Within the group of fertile couples, time to pregnancy was predicted by the husbands' above-cited factor and by the wives' frequency of thoughts and concerns related to the desired child. The results support the conclusion that in both women and men, psychological factors specifically related to the project of conceiving a child are significant predictors of the couple's fertility status.

Cognitive assessment of school-age children infected with maternally transmitted human immunodeficiency virus type 1.

Thirty-three children vertically infected with human immunodeficiency virus type 1 (HIV-1), who were born before 1985, were followed in a single center, and had reached the age of 6 years, were studied and tested for school achievement. Of these 33 children, 24 were also tested for cognitive abilities, fine motor and language skills, and emotional adaptation. Of the 33 patients, 22 (67%) had normal school achievement at a mean age of 9.5 +/- 1.6 years. The mean IQ was 95 +/- 11, but 54% of the patients (13/24) had abnormal results on visual-spatial and time orientation tests, 44% had speech and/or language delay or articulation disorders, and 29% of the children and 42% of the parents had psychoaffective disturbances of intermediate or high severity. Normal school performance was positively correlated with results of the different cognitive tests and to a lesser extent with the absence of psychoaffective symptoms, but was independent of the mode of maternal infection or the parents' educational level. Children with normal school achievement had a higher percentage of circulating CD4+ lymphocytes during the course of infection. We conclude that children whose HIV-1 infection is maternally acquired have better cognitive abilities and school achievement than was initially thought, and that the percentage of circulating CD4+ lymphocytes during the first years of life appears to be predictive of future school adaptation or cognitive abilities.

Morbidity and mortality in European children vertically infected by HIV-1. The French Pediatric HIV Infection Study Group and European Collaborative Study.

Based on 392 infected children enrolled in two European prospective studies of infants born to HIV-infected women, with similar standard protocols, HIV disease progression in the first 6 years of life is described, using the 1994 CDC paediatric HIV classification. Most children had developed minor (A) or moderately severe (B) illness in the first 4 years of life, although usually it was transient in nature. Progression to U.S. Centers for Disease Control and Prevention (CDC) group C disease or HIV-related death is an estimated 20% (95% confidence interval 16-24%) during the first year of life, and 4.7% (3.3-6.5%) per year thereafter, giving a cumulative incidence of 36% (30-43%) by 6 years. The mortality rate at 6 years is 26% (20-32%). Two thirds of the children alive at 6 years had only minor symptoms, and one third had a CD4+ cell distribution of > 25% despite previous clinical manifestations and a transient period of moderate immune deficiency. Differences in zidovudine monotherapy between the two cohorts were not associated with the mortality rate. However, the risk of severe bacterial infections was lower in the French cohort, in which the use of antibacterial prophylaxis was more common. The early, severe form of HIV disease affects approximately 20% of infants, and after 6 years 75% of infected children are still alive. This has important implications for health-care planning.

Relation of the course of HIV infection in children to the severity of the disease in their mothers at delivery.

BACKGROUND: Among infants with maternally transmitted human immunodeficiency virus (HIV) infection, there are two patterns of disease progression. In about a fifth of these infants there is a rapid progression to profound immunodeficiency, whereas in the majority the disease progresses much more slowly. METHODS: We studied the clinical and biologic characteristics of the mothers of infants infected with HIV type 1 (HIV-1) in the French Prospective Multicenter Cohort. Infection in the children was confirmed by serologic tests at the age of 18 months or by death from the acquired immunodeficiency syndrome at an earlier age. Only the 162 infected infants who could be followed for at least 18 months or until death were included in the analysis. RESULTS: The risk of opportunistic infections or encephalopathy in the first 18 months was 50 percent in the infants of mothers with class IV disease, according to the Centers for Disease Control and Prevention classification, and 14 percent in the infants of mothers with class II or III disease (relative risk, 3.6; 95 percent confidence interval, 1.8 to 7.3; P < 0.002). Forty-four percent of the former infants and 9 percent of the latter died before 18 months (relative risk, 4.7; 95 percent confidence interval, 2.1 to 10.4; P < 0.002). The risk of death correlated inversely with the mother's CD4+ cell count and directly with her HIV-1 p24 antigen level at delivery. There was also a direct correlation between the mother's CD4+ cell count and that of the infant at one, three, and nine months of age (correlation coefficient at nine months [n = 44], 0.48; P < 0.002). HIV-1 p24 antigen was detected more often in the infants whose mothers also had the antigen. CONCLUSIONS: In infants whose HIV infection is maternally acquired, the rate of disease progression varies directly with the severity of the disease in the mother at the time of delivery.

CCR5 chemokine receptor variant in HIV-1 mother-to-child transmission and disease progression in children. French Pediatric HIV Infection Study Group.

CONTEXT: Studies suggest that adults with the CCR5delta32 deletion are less likely to become infected with the human immunodeficiency virus (HIV) and to develop HIV-related disease progression, but the effect of the mutation in children is not known. OBJECTIVE: To study the effect of the CCR5 chemokine receptor mutant allele on mother-to-child transmission of HIV type 1 (HIV-1) and subsequent disease progression in infected children. DESIGN: Multicenter, prospective study of infants born to mothers seropositive for HIV-1. SETTING: A total of 52 medical centers participating in the French Pediatric HIV Cohort studies. PARTICIPANTS: The CCR5delta32 deletion was studied in 512 non-African children, born between 1983 and 1996 to HIV-1-infected mothers. Among them, 276 children were infected and 236 were not. MAIN OUTCOME MEASURES: HIV-1 infection status and, in infected children followed up since birth, incidence of category B and C disease events and severe immunosuppression as defined in the new pediatric Centers for Disease Control and Prevention (CDC) classification, according to CCR5 genotype. RESULTS: The 32-base pair deleted allele was detected at a frequency of 0.05. Only 1 infant, not infected by HIV-1, was homozygous for the delta32 deletion. The 49 heterozygous children (9.6% of the total; 95% confidence interval [CI], 7.1-12.2) were equally distributed into the infected (9.8%) and uninfected (9.3%) groups. The incidence of stage C symptoms in heterozygous infected children was 9% at 36 months vs 28% in children homozygous for the normal allele (P<.004). The proportion of children at 8 years old with no stage B or C symptoms was 49% for heterozygous children and 11% for children homozygous for the normal allele (P<.003). The progression of severe immune deficiency (CD4 <15%, CDC stage 3) was also significantly different between the 2 groups (P<.001). CONCLUSIONS: Heterozygosity for the CCR5delta32 deletion does not protect children from infection by the maternal virus but substantially reduces the progression of the disease in HIV-1-infected children.

Impact of heterozygosity for the chemokine receptor CCR5 32-bp-deleted allele on plasma virus load and CD4 T lymphocytes in perinatally human immunodeficiency virus-infected children at 8 years of age.

The CCR5 gene encodes one of the major human immunodeficiency virus type 1 (HIV-1) coreceptors. A 32-bp deletion in this gene (delta ccr5) is associated with relative resistance to disease progression in heterozygous HIV-1-infected persons. The effect of this mutation on virologic and immunologic parameters was determined in a cohort of 45 perinatally HIV-1-infected children prospectively followed after 5 years of age. At a median age of 8.3 years, heterozygous children had significantly lower virus load than homozygous children (median, 3.3 vs. 4.1 log copies/mL, P < .009) and higher percentages of CD4 T cells (median, 26% vs. 17%, P < .07). However, there was no discernible influence of the CCR5 genotype on the percentages of CD8 T cells (P < .27) or on HIV-specific cytotoxic T lymphocyte activities (P < .65). There was a trend for lower rates of progression to AIDS (CDC stage C) in heterozygous children. These data confirm a major role for the CCR5 coreceptor in HIV-1 pathogenesis in children.

CCR2B-64I chemokine receptor allele and mother-to-child HIV-1 transmission or disease progression in children. French pediatric HIV infection study group.

The beneficial role of a variant of the chemokine receptor CCR2B (CCR2B-641) in the evolution of HIV-1 infection in adults is still controversial. Furthermore, no studies have been performed in HIV-1-infected children. A multicenter and prospective study of 745 infants born to HIV-1-seropositive mothers was performed. The CCR2B-641 allele was studied in 525 non-African children among whom 523 had been previously genotyped for the CCR5delta32 allele and 220 African children. Of the 745 total, 376 children were infected and 369 were uninfected. In the complete population studied, the children homozygous for the CCR2B-64I allele and the heterozygous children were found distributed equally in the infected (respectively, 1.6% and 21%) and uninfected (respectively, 1.9% and 26.3%) groups (p < .22). Among 376 infected children, the incidence of stage C symptoms (U.S. Centers for Disease Control and Prevention [CDC] classification) or the progression of severe immune deficiency (CD4 <15%, CDC stage 3) was not significantly different in heterozygous infected children or children homozygous for the normal allele (p < .17 and p < .75, respectively). The same lack of protective effect was obtained when a separate analysis was performed in the non-African and African HIV-1-infected children.

Neonatal characteristics in rapidly progressive perinatally acquired HIV-1 disease. The French Pediatric HIV Infection Study Group.

OBJECTIVE: To identify clinical and laboratory parameters at birth that are associated with the rapidly progressive form of human immunodeficiency virus type 1 (HIV-1) disease in children born to infected mothers. DESIGN: Multicenter, prospective study of infants born to HIV-seropositive mothers. SETTING: A total of 62 obstetric and pediatric centers in France. PARTICIPANTS: Of 1386 children born to HIV-1-seropositive mothers at least 18 months before the cutoff date, 267 were infected. Infection was defined as serological positivity at 18 months or death from HIV disease before the age. MAIN OUTCOME MEASURE: Category C events (including opportunistic infections, recurrent severe bacterial infections, cancers, specific encephalopathy, and wasting syndrome) in the new pediatric Centers for Disease Control and Prevention classification during the first year of life, according to clinical, immunological, and virological findings at birth. RESULTS: The risk of category C manifestations at 12 months was significantly higher when an infected newborn had liver and/or spleen enlargement and/or adenopathies (38.1% vs 15.1%; relative risk [RR], 2.5; 95% confidence interval [CI], 1.4 to 6.0; P<.02) or a low proportion (<30%) of CD4+ cells at birth (45.5% vs 15.0%; RR, 3.0; 95% CI, 1.4 to 6.4; P<.005). Similarly, HIV-1 culture and/or polymerase chain reaction positivity during the first week of life was associated with a higher risk of the early, severe form of HIV infection (26.4% vs 9.3%; RR, 2.8; 95% CI, 1.3 to 6.1; P<.006). In case of positive antigenemia at birth, the risk was 50.0% vs 14.4% (RR, 3.5; 95% CI, 1.9 to 6.2; P<.001). These parameters, determined at birth, were strongly interrelated and could reflect active disease onset in utero in some cases of early, severe HIV-1 disease in childhood. CONCLUSIONS: These prognostic markers, particularly virological parameters, are of value in monitoring children infected by HIV and might serve as a basis for early therapeutic intervention.

Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml.

In a collaboration of 7 European and United States prospective studies, 44 cases of vertical human immunodeficiency virus type 1 (HIV-1) transmission were identified among 1202 women with RNA virus loads <1000 copies/mL at delivery or at the measurement closest to delivery. For mothers receiving antiretroviral treatment during pregnancy or at the time of delivery (or both), there was a 1.0% transmission rate (8 of 834; 95% confidence interval [CI], 0.4%-1.9%), compared with 9.8% (36 of 368; 95% CI, 7.0%-13.4%) for untreated mothers (risk ratio, 0.10; 95% CI, 0.05-0.21). In multivariate analysis adjusting for study, transmission was lower with antiretroviral treatment (odds ratio [OR], 0.10; P<.001), cesarean section (OR, 0.30; P=.022), greater birth weight (P=.003), and higher CD4 cell count (P=.039). In 12 of 44 cases, multiple RNA measurements were obtained during pregnancy or at the time of delivery or within 4 months after giving birth; in 10 of the 12 cases, the geometric mean virus load was >500 copies/mL. Perinatal HIV-1 transmission occurs in only 1% of treated women with RNA virus loads <1000 copies/mL and may be almost eliminated with antiretroviral prophylaxis accompanied by suppression of maternal viremia.

Acceptability and impact of zidovudine for prevention of mother-to-child human immunodeficiency virus-1 transmission in France.

We studied the propagation and the impact of zidovudine prevention on the human immunodeficiency virus-1 transmission rate from infected mothers to their infants in the French nationwide prospective cohort. Infection was diagnosed in the children on the basis of at least two positive human immunodeficiency virus-1 polymerase chain reaction tests, culture, or both. The transmission rate among treated women was compared with that among untreated women during the same period and with that among women enrolled in the cohort since 1986. The impact of zidovudine was analyzed according to the women's clinical and biologic characteristics, the mode of delivery, and use of zidovudine therapy before the pregnancy. Nearly 90% of women were treated as soon as the second half of 1994. In 1994 and 1995, 80% of mother-child pairs received at least one of the three phases of preventive treatment. Among the 663 mothers enrolled during these 2 years, only six refused the treatment. Zidovudine treatment was associated with a reduction in the transmission rate of nearly two-thirds, from 14% +/- 6% to 5% +/- 2% (p < 0.01). The degree of reduction was not influenced by the maternal CD4+ cell count or p24 antigenemia at delivery. Zidovudine treatment of the mother before the pregnancy considerably reduced the impact of preventive therapy; the transmission rate was significantly higher among pretreated mothers (20% versus 5%, p < 0.01) even after adjusting for maternal CD4+ cell count. Zidovudine prevention is now widely used in France and has had a major impact on the epidemiology of mother-child human immunodeficiency virus transmission. This justifies a policy of offering human immunodeficiency virus screening to all women before or shortly after the diagnosis of pregnancy.